Akinari Tabaru

University of Occupational and Environmental Health, Kitakyūshū, Fukuoka-ken, Japan

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Publications (56)211.83 Total impact

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    ABSTRACT: Aim:  Non-hepatitis B virus/non-hepatitis C virus-related hepatocellular carcinoma (NBNC-HCC) is often detected at an advanced stage, and the pathology associated with the staging of NBNC-HCC remains unclear. Data mining is a set of statistical techniques which uncovers interactions and meaningful patterns of factors from a large data collection. The aims of this study were to reveal complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC-HCC using data mining techniques.Methods:  A database was created from 663 patients with NBNC-HCC at 20 institutions. The Milan criteria were used as staging of HCC. Complex associations of variables and clinical feature profiling with the Milan criteria were analyzed by graphical modeling and decision tree algorithm methods, respectively.Results:  Graphical modeling identified six factors independently associated with the Milan criteria: diagnostic year of HCC; diagnosis of liver cirrhosis; serum aspartate aminotransferase (AST); alanine aminotransferase (ALT); α-fetoprotein (AFP); and des-γ-carboxy prothrombin (DCP) levels. The decision trees were created with five variables to classify six groups of patients. Sixty-nine percent of the patients were within the Milan criteria, when patients showed an AFP level of 200 ng/mL or less, diagnosis of liver cirrhosis and an AST level of less than 93 IU/mL. On the other hand, 18% of the patients were within the Milan criteria, when patients showed an AFP level of more than 200 ng/mL and ALT level of 20 IU/mL or more.Conclusion:  Data mining disclosed complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC-HCC.
    Hepatology Research 04/2011; 41(6):564 - 571. · 2.07 Impact Factor
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    ABSTRACT: A 71-year-old male patient was diagnosed with rheumatoid arthritis (RA) in 2000. Various disease-modifying anti-rheumatic drugs (DMARDs) and an anti-tumor necrosis factor biologic etanercept were administrated, but were unable to control the disease activity of RA. He was then diagnosed with rheumatoid vasculitis and received a total of 3 courses of an anti-interleukin-6 receptor antibody, tocilizumab. After the 3 courses of tocilizumab therapy, ascites and renal dysfunction gradually appeared and he was admitted to our hospital. Biochemical data suggested that he had developed decompensated liver cirrhosis. His renal function deteriorated rapidly, and he died 9 days after the admission. Serum aminotransferase levels had been relatively low during the treatment with tocilizumab, however, autopsy showed marked atrophy of the liver. Immunohistochemical analysis revealed that the hepatocytes had fallen into apoptosis and that hepatic regeneration had been extremely suppressed. Although molecular target drugs such as tocilizumab are being widely used and are important emerging treatment options in adult patients with moderate to severe RA, these drugs could induce liver failure by inhibiting liver regeneration as in this case. Physicians need to stay alert to the impact of these drugs on liver regeneration and should follow up with ultrasonography or computed tomography.
    Hepatology Research 03/2011; 41(5):492-6. · 2.07 Impact Factor
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    ABSTRACT: A 50-year-old woman was referred to our hospital due to liver dysfunction and progressive neurological symptoms. She had previously been diagnosed with nonalcoholic steatohepatitis (NASH). Ursodeoxycholic acid (UDCA) had effectively normalized her serum aminotransferase levels, however, she presented with loss of balance, dysarthria and difficulty in handwriting. Autoantibodies and hepatitis virus markers were negative. Serum ceruloplasmin and copper levels were noted to be 9 mg/dL and 32 µg/dL, respectively. The 24-h urinary copper excretion was 331.8 µg/day. Kayser-Fleischer ring was demonstrated. Histological examination of the liver revealed inflammatory infiltrate and fibrosis, and the hepatic copper concentration was 444.4 µg/g dry weight. We diagnosed her as having Wilson disease and started treatment with trientine. Immuohistochemistry for keratin 8 and p62 demonstrated Mallory-Denk bodies. Many of the p62-expressing cells were positive for 4-Hydroxy-2-nonenal (HNE). Few Ki-67-positive hepatocytes were present in the liver. Wilson disease is one of the causes of NASH and UDCA may be a supportive therapeutic agent for Wilson disease. Cell proliferation is suppressed under copper-loaded conditions and this phenomenon may be associated with the clinical course of Wilson disease.
    Hepatology Research 02/2011; 41(3):270 - 276. · 2.07 Impact Factor
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    ABSTRACT: Giant cell hepatitis is rare in adult patients. This form of hepatitis shows fast progression to cirrhosis. A 65-year-old woman was admitted to our hospital with jaundice. She was negative for hepatitis virus markers and positive for antinuclear antibodies. We diagnosed her as autoimmune hepatitis. Liver biopsy findings revealed typical features of interface hepatitis and giant cell hepatitis. Giant cells were positive for keratin 8/18, but not for keratin 19, keratin 7 or Ki-67. These results suggest that giant cell formation is associated with the fusion of matured hepatocytes rather than the active proliferation of immature cells.
    Internal Medicine 01/2011; 50(4):315-9. · 0.97 Impact Factor
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    ABSTRACT: We describe a case of a 69-year-old woman who developed rapidly progressive hepatocellular carcinoma (HCC) associated with autoimmune hepatitis (AIH) after a 7-year follow-up. Markers for viral hepatitis were negative. Serum tumor markers including alpha-fetoprotein and prothrombin induced by vitamin K absence II rose suddenly, and a large tumor was detected in spite of regular surveillance for HCC. Surgical treatment was performed. The resected liver specimen revealed well to moderately differentiated HCC. Ki67 staining showed rapid proliferation of the HCC. Although the incidence of HCC in patients with AIH has been unclarified, the possible complication by HCC must not be overlooked.
    Internal Medicine 01/2011; 50(13):1409-13. · 0.97 Impact Factor
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    ABSTRACT: A 37-year-old man was diagnosed with Wilson disease at the age of 14. His first manifestations were neurological. He was treated with trientine for more than 10 years and suffered from anemia and liver dysfunction. Wilson disease is a genetic disorder characterized by accumulation of copper in the body. Excess copper is toxic, but copper is an essential trace element. Copper-binding ceruloplasmin is important for iron metabolism. Excess copper chelating treatment-induced anemia and iron deposition in the liver was suspected. Proper monitoring of copper status is important for the management of Wilson disease.
    Internal Medicine 01/2011; 50(14):1461-4. · 0.97 Impact Factor
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    ABSTRACT: Metastatic malignant melanoma (MM) of the liver evolving into acute hepatic failure is a rare occurrence. We describe the case of an 82-year-old man with a history of MM on the left thumb treated with amputation and chemotherapy 40months previously. On admission, he had abdominal pain, weight loss, lethargy and jaundice. Radiologic investigations such as enhanced computed tomography and abdominal ultrasound failed to establish an etiologic diagnosis. A liver biopsy revealed amelanotic melanoma cells diffusely infiltrating the hepatic parenchyma. His liver injury progressed and the patient died of hepatic failure on the 13th hospital day. Autopsy revealed >70% infiltration by metastatic amelanotic melanoma in the liver. KeywordsAmelanotic melanoma-Liver metastasis-Acute hepatic failure
    Clinical Journal of Gastroenterology 01/2010; 3(6):327-331.
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    ABSTRACT: A 59-year-old male patient underwent surgical treatment for non-Hodgkin’s lymphoma of the right scrotum in October 2007. He received a total of 4 courses of two different adjuvant chemotherapy regimens including rituximab from January to April 2008. In June 2008 he was hospitalized due to severe liver dysfunction with an alanine aminotransferase of 2039IU/l and a prothrombin time of 23.3%. He was diagnosed with acute hepatitis C by the detection of hepatitis C virus (HCV) RNA and negative anti-HCV antibody, and his hepatic function improved with bed rest during hospitalization; however, the production of anti-HCV antibodies was not detected until January 2009. Severe liver dysfunction is uncommon among patients with acute hepatitis C, and the long window (8months) between HCV infection and the development of anti-HCV antibodies observed in the present case may have been due, at least in part, to a B cell disorder caused by rituximab therapy. In addition to the well-known risk of reactivation of hepatitis B virus infection in patients undergoing chemotherapy, physicians should be aware of the potential effects of chemotherapy on the clinical course of HCV infection. KeywordsAcute hepatitis-Hepatitis C virus-Humoral immunity-Rituximab
    Clinical Journal of Gastroenterology 01/2010; 3(5):254-258.
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    ABSTRACT: Serum levels of soluble interleukin-2 receptor (sIL-2R) are known to serve as a marker for the activation of T lymphocytes. We measured serum levels of sIL-2R in patients with chronic hepatitis C (CHC) during interferon (IFN)-based treatment to determine the correlation between those levels and therapeutic efficacy, and to clarify whether there is a difference in the activation of T lymphocytes among HCV genotypes after the treatment. Forty-four patients received IFN-alpha2b monotherapy (group IFN-M), whereas 82 patients received the combination therapy with IFN-alpha2b and ribavirin (group IFN+R). We measured serum sIL-2R levels in these patients before (T0) and 2 weeks (T2) after the treatment. The sustained virologic response rates in genotype 2a/2b patients were significantly higher than those in genotype 1b patients in both groups (P<0.005). In sustained virologic responders, sIL-2R levels at T2 were significantly higher than those at T0 in both groups (P<0.001). In nonresponders, sIL-2R levels at T2 were not different from those at T0 in group IFN-M, but were significantly higher than those at T0 in group IFN+R (P=0.0072). In genotype 1b patients, sIL-2R levels at T2 were not different from those at T0 in group IFN-M, but were significantly higher than those at T0 in group IFN+R (P=0.0064). In genotype 2a/2b patients, sIL-2R levels at T2 were significantly higher than those at T0 in both groups (P<0.0005). These findings suggest that the activation of T lymphocytes after IFN-based treatment contributes to a high-sustained virologic response rate, especially in genotype 2a/2b patients.
    European Journal of Gastroenterology & Hepatology 06/2008; 20(5):373-8. · 1.92 Impact Factor
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    ABSTRACT: Liver steatosis is frequently observed in patients with chronic hepatitis C (CHC) and is an identified risk factor for progression of liver fibrosis. This study aimed to evaluate the relationship between steatosis and host/viral factors, and the correlation between steatosis and insulin secretion in CHC patients with normal glucose tolerance (NGT). A total of 212 CHC patients were enrolled in this study. Insulin resistance and insulin secretion were determined in response to oral loading of 75 g glucose. Liver fibrosis and steatosis were quantified by the image analysis. Of the 212 CHC patients, 165 (78%) had steatosis, mostly of a mild degree. Multiple ordinal regression analysis revealed body mass index (BMI) (P= 0.011) as the main factor associated with severe steatosis. Of the 212 CHC patients, 148 (61%) showed NGT, and the serum insulin response to oral glucose loading in these NGT patients with steatosis was significantly different from that in patients with NGT but no steatosis. The peak insulin response occurred at 60 min in cases of mild steatosis, and at 90 min in patients with moderate or severe steatosis. The insulin level at 120 min in patients with severe steatosis was higher than that in those without steatosis. The total area under the response curve of insulin during OGTT in the patients with steatosis is higher than that in those without steatosis. Exaggerated insulin secretion was observed even in CHC patients with mild steatosis and NGT, suggesting the presence of insulin resistance. Exaggerated insulin secretion may accelerate the progression of liver fibrosis in CHC patients.
    The American Journal of Gastroenterology 11/2007; 102(10):2173-80. · 7.55 Impact Factor
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    ABSTRACT: Although many workers suffer from chronic hepatitis, the influence of labor on its clinical course is not clear. We prospectively followed 89 workers with chronic hepatitis for 3 years, and examined the relationship between job-related factors, such as job class, job type, working hours and work effort, and the liver function test. There were no job-related factors that had any influence on the activity of hepatitis. Moreover, no significant relationship was found between job-related factors, including tiredness, and the acute exacerbation of hepatitis. No significant changes of aminotransferase levels and of platelet counts divided by each job-related factor were found during the observation period, but the platelet counts decreased in workers with acute exacerbation, but without clinical significance. These results suggest that job-related factors have little influence on the clinical course of chronic hepatitis during a relatively short observation period.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 09/2007; 104(8):1192-203.
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    ABSTRACT: This is a report of a case of hepatocellular carcinoma (HCC) with gastric metastasis and a review of 20 cases of gastric metastasis of HCC in Japan. A 67-year-old man was diagnosed as having HCC in May 1991, and underwent transcatheter arterial embolization in June 1991 and February 1992. He came to us with hematemesis in November 1992. An endoscopic examination revealed a semipedun-culated polypoid lesion with bleeding spots at the fornix of the stomach. The polypoid lesion was resected by endoscopic snare polypectomy to prevent rebleeding and in order to make a definitive diagnosis. Histological examination of the resected specimen, 15X10X6 mm in size, revealed well-differentiated HCC with bile production.
    Digestive Endoscopy 08/2007; 6(3):248 - 252. · 1.61 Impact Factor
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    ABSTRACT: Premedication with glucagon or hyoscyamine is reported to be effective in reducing colonic spasm. However, these drugs can be associated with unfavorable events. This prospective study was designed to compare the effects of premedication with glucagon with those of scopolamine butylbromide on cardiopulmonary parameters, intubation time, and patient discomfort in unsedated patients undergoing diagnostic colonoscopy. One hundred consecutive adult patients (65 males) undergoing colonoscopy without sedation were randomized to receive 1 mg of glucagon (n = 50) or 20 mg of scopolamine butylbromide (n = 50), intramuscularly. Physiologic changes, including systolic blood pressure, heart rate, and oxygen saturation, were monitored before colonoscope insertion and at three-minute intervals during colonoscopy. The percentages of completed procedure and time to cecal intubation were recorded. Patients were asked to rate pain by using a five-point pain score (0 = no pain; 4 = severe pain). The percentages of completed procedure (96 vs. 98 percent), time to cecal intubation (16.3 vs. 14.5 minutes), and pain score (1.7 vs. 1.5) did not differ significantly between two groups. An increase in heart rate of more than ten beats per minute from baseline during colonoscopy occurred significantly more often in scopolamine group (44 percent of 50 patients) than in the glucagon group (12 percent of 50 patients; P = 0.0004). There were no significant differences between the two study groups with regard to changes in systolic blood pressure and decrease in oxygen saturation during colonoscopy. Premedication with 1 mg of glucagon facilitates favorable examination with respect to physiologic changes compared with 20 mg of scopolamine. These features favor glucagon as the preferred premedication for patients undergoing colonoscopy.
    Diseases of the Colon & Rectum 10/2006; 49(9):1393-8. · 3.34 Impact Factor
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    ABSTRACT: The aim of the present study was to determine whether a 24-week course of combination therapy with ribavirin and high-dose interferon-alpha2b (IFN-alpha2b) could provide an acceptable treatment efficacy in chronic hepatitis C (CHC). Seventy-six patients with CHC whose serum hepatitis C virus (HCV) RNA levels were more than 100 kIU/mL on quantitative polymerase chain reaction (PCR) assay were included. The patients were assigned to two different dose groups of IFN-alpha2b: group A (n = 39) received 6 MU and group B (n = 37) received 10 MU. Each group received the dose daily for 14 days then three times per week for a total of 24 weeks. In addition, HCV genotype 1b patients in group A and group B were classified into group C (n = 20) and D (n = 29), respectively. All patients received 600 or 800 mg ribavirin per day. Sustained response rates in group A were significantly higher than those in group B (66.7%vs 35.1%, intent-to-treat, P = 0.0060). However, sustained response rates in group C were not different from those in group D (45.0%vs 20.7%, intent-to-treat, P = 0.0696). The proportion of patients who discontinued the treatment or reduced drug dosage because of adverse events was significantly higher in group B than in group A (27.0%vs 7.69%, P = 0.0224). A 24-week course of combination therapy with ribavirin and 6 MU IFN-alpha2b had an acceptable efficacy with fewer adverse events than that with ribavirin and 10 MU IFN-alpha2b in CHC.
    Journal of Gastroenterology and Hepatology 02/2006; 21(1 Pt 2):308-12. · 3.33 Impact Factor
  • Gastrointestinal Endoscopy 07/2005; 61(7):918-9. · 5.21 Impact Factor
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    ABSTRACT: The efficacy of interferon (IFN)-based antiviral therapy for chronic hepatitis C (CHC) varies depending on predictive factors such as hepatitis C virus (HCV) genotype and viral load. For patients with good predictive factors, a low dose and short course of IFN-based therapy may be adequate. However, there is no evidence about the optimal duration of IFN-based therapy for these patients. The aim of this study was to clarify whether the duration of IFN therapy could be shortened to less than the conventional treatment period for patients with good predictive factors. A total of 25 treatment-naive CHC patients with genotype 2a were randomized to receive either IFN monotherapy for 24 wks (group A: long-term IFN therapy, n = 13) or for 6 wks (group B: short-term IFN therapy, n = 12). Patients were monitored for HCV RNA and routine liver function tests during and following treatment, and data were examined according to intention-to-treat analysis. Eleven of 13 patients in group A and all patients in group B completed IFN therapy according to the original planned schedule. At the end of the treatment, viral clearance occurred in all patients. However, 4 patients in group A and 5 in group B relapsed within 6 months of follow-up. There was no significant difference of sustained response rate between group A (53.8%) and group B (58.3%). Among patients who had HCV viral load of <100 kIU/ml, the sustained response rate was 83.3% (5/6) in group A and 100% (5/5) in group B. In this study, our results suggest that the duration of IFN therapy can be shortened to less than 24 wks in patients with good predictive factors. Further studies, however, should examine the optimal regimen of IFN therapy based on the backgrounds of patients.
    The American Journal of Gastroenterology 04/2005; 100(4):862-7. · 7.55 Impact Factor
  • Gastrointestinal Endoscopy - GASTROINTEST ENDOSCOP. 01/2005; 61(5).
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    ABSTRACT: Diabetes mellitus (DM) is frequently observed in patients with chronic hepatitis caused by hepatitis C virus infection (CHC). The present study was designed to determine the pathogenic factors responsible for glucose intolerance in CHC patients. A total of 131 patients with CHC were enrolled in this study. Insulin resistance and beta-cell function were determined after 75 g oral glucose tolerance tests. Glucose intolerance was detected in 27.5% (36/131) of CHC patients; 10 had DM and 26 impaired glucose tolerance. HOMA-R [insulin 0xglucose 0/22.5] was greater in patients with both impaired glucose tolerance and DM than in those with normal glucose tolerance (P<0.01). Matsuda index [10(4)/ (square root) (mean insulinxmean glucosexglucose 0xinsulin 0)] was lower in diabetic patients than in those with normal glucose tolerance (P<0.05). The insulinogenic index [Deltainsulin 30-0/Deltaglucose 30-0] and DeltaC-peptide 30 [DeltaC-peptide 30-0/Deltaglucose 30-0] were significantly lower even in patients with impaired glucose tolerance than in patients with normal glucose tolerance (P<0.01). Both insulin resistance and beta-cell dysfunction contribute to glucose intolerance in CHC patients.
    Journal of Hepatology 08/2004; 41(1):132-8. · 9.86 Impact Factor
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    ABSTRACT: We evaluated whether early changes in serum levels of fibrogenic markers during interferon (IFN) treatment can predict long-term anti-fibrogenic effects in patients with chronic hepatitis C (CHC). We retrospectively examined the serum levels of N-terminal peptide of type III procollagen (P-III-NP) and 7S domain of type IV collagen (IV-7S) in 56 patients with CHC who were revealed to be IFN-nonresponders. We measured these markers before (T0) and 1 month (T1) after the commencement of IFN therapy, at the end of 24 weeks' IFN therapy (T24), and 1 year (T24-1) and more than 2 years (T24-2) after the cessation of IFN therapy. We also measured these markers twice, at intervals of more than 2 years, in 43 IFN-untreated patients with CHC as controls. In nonresponders, both P-III-NP and IV-7S levels at T24-2 were significantly decreased compared with those at T0. P-III-NP levels at T1 were significantly decreased compared with those at T0, and remained at significantly low levels until the end of the observation period. IV-7S levels at T1 were not significantly different from those at T0. In patients whose IV-7S levels at T24-2 were decreased compared with those at T0, IV-7S levels at T1 were significantly lower than those at T0. In patients whose IV-7S levels at T24-2 were elevated or unchanged compared with those at T0, IV-7S levels at T1 were significantly higher than those at T0. In untreated patients, both P-III-NP and IV-7S levels at more than 2 years after the initial time were significantly increased compared with those at the initial time. An early decrease in IV-7S levels after IFN treatment is a useful indicator of anti-fibrogenic effects in nonresponders.
    Journal of Gastroenterology 02/2004; 39(3):247-54. · 3.79 Impact Factor
  • Gastrointestinal Endoscopy - GASTROINTEST ENDOSCOP. 01/2004; 59(5).